We are studying the cellular and molecular basis of autoimmune diseases with two purposes. First, we want to establish the pathogenic role and antigen-specificity of T cells that cause autoimmune diseases such as multiple sclerosis, myasthenia gravis, insulin-dependent diabetes, among others. Second, we would like to determine the feasibility of specific antigen-induced apoptosis as a means of treating such autoimmune diseases. To these ends, we have made progress in the following areas: 1) we have employed the marmoset model of experimental allergic encephalomyelitis to show that determinant spreading is an important event in generating immune responses that cause damage to the myelin sheath; 2) we found that repeated administration of a protein component of the insulating sheath (myelin) of nerves in the central nervous system dampens the immune response and improves clinical outcome in marmosets; 3) we are continuing to progress towards a clinical trial of antigen-induced apoptosis in multiple sclerosis, and 4) we have created a transgenic mouse model of myasthenia gravis which has a powerful response to a peptide from the acetylcholine receptor. As part of these studies we are also trying to understand the regulation of antigen-induced death by T cell receptor stimulation. These studies should yield important new insights into the pathogenesis and treatment of autoimmune diseases which is a widespread health problem in the U.S. particularly among working women. - Autoimmunity, multiple sclerosis, myastenia gravis